The cytologic diagnosis of metastatic adenocarcinoma in effusions can be very difficult. Not only can malignant cells have very bland cytologic features but reactive mesothelial cells can assume a very atypical appearance. Using the avidin-biotin immunoperoxidase technique on cytospin preparations of pleural and peritoneal effusions, we investigated the reactivity of purified monoclonal antibody B72.3 with benign and malignant effusions. Initial effusion specimens studied were carefully selected to include only cytologically malignant effusions from patients with a history of adenocarcinoma and cytologically benign effusions from patients with no history of adenocarcinoma. Of the 25 malignant effusions studied, 20-90% of the cells demonstrated strongly positive staining with B72.3. There was no detectable staining of cells in reactive effusions. We conclude that immunostaining with B72.3 is useful in the cytologic diagnosis of metastatic adenocarcinoma in effusions.